A very interesting article.Problem with population studies concerning elderly getting flu vaccine was that the major confounding variable, frailty
was not controlled for.Frail elder are less likely to get vaccinated and more
likely to die from the flu—they are also less likely to go to the doctor. Thus all the past studies had over represented
the frail unvaccinated group.Those who got vaccinated were less likely to die
because they were healthier—not because of the vaccine.Moreover, a study
which used incidents of cancer and heart disease as a marker for frail also failed because those who weren’t frail were
more likely to go to the doctor and thus be recorded as having these conditions.

Three studies set the record straight.A double blind study was done in 1994 which showed little benefit for the vaccine in preventing deaths.Finally, a recent study based on frailty markers of lung function, the ability to
bathe and dress, and use of certain medication, this study found that vaccination had little effect on older people’s
risk for pneumonia—the most dangerous complication of influenza.The reason
for the failure of the vaccine was found in another recent study where the elderly need 4 times the amount of antigens given
in a standard dose to produce the immune response as a healthy adult under 40.

Doubts Grow Over Flu
Vaccine in Elderly

September 2, 2008, by Brenda Goodman, New York Times

The influenza vaccine, which has been strongly recommended for people over
65 for more than four decades, is losing its reputation as an effective way to ward off the virus in the elderly. A growing number of immunologists and epidemiologists say the vaccine probably does
not work very well for people over 70, the group that accounts for three-fourths of all flu deaths. The latest blow was a study in The Lancet last month that called into question much
of the statistical evidence for the vaccine's effectiveness.

The authors said previous studies had measured the wrong
thing: not any actual protection against the flu virus but a fundamental difference between the kinds of people who get vaccines
and those who do not. This contention is far from universally
accepted. And even skeptics say that until more effective measures are found, older people should continue to be vaccinated,
because some protection against the flu is better than none.

Still, the Lancet article has reignited a longstanding
debate over claims that the vaccine prevents thousands of hospitalizations and deaths in older people. "The whole notion of
who needs the vaccine and why is changing before our eyes," said Peter Doshi, a doctoral candidate at M.I.T. who published
a paper on the historical impact of influenza in May in The American Journal of Public Health. The Lancet paper, by Michael L. Jackson and colleagues at the Group Health
Center for Health Studies in Seattle, was based on an analysis of medical charts of thousands of elderly members of an H.M.O.
The study found that people who were healthy and conscientious about staying well were the most likely to
get an annual flu shot. Those who are frail may have trouble bathing or dressing on their own and are less likely to get to
their doctor's office or a clinic to receive the vaccine. They are also more likely to be closer to death.

Dr. David K. Shay of the Centers for Disease Control and
Prevention, a co-author of a commentary that accompanied Dr. Jackson's study, agreed that these measures of health and frailty
"were not incorporated into early estimations of the vaccine's effectiveness" and could well have skewed the findings.

Not everyone is sold on the significance of the Lancet
study. "I think this is another study that provides interesting findings and raises questions," said Dr. Kristin Nichol, chief
of medicine at the Veterans Affairs hospital in Minneapolis. "I don't think we know yet what the final word is on influenza
vaccinations in the elderly. “ "I really feel, and I feel very strongly about this, that the
public health message should be that vaccines are effective," she continued. "I don't think that science is necessarily best
hashed out in the media."

Dozens of studies since 1960 have supported the view that
the vaccine is a powerful protector of the elderly, cutting their risk of dying in winter from any cause by almost 50 percent
and reducing the risk of hospitalization by nearly 30 percent. Those
findings came from observational studies, in which scientists make inferences about the effect of a treatment on a population
by comparing what happens to a group that has the treatment with what happens to an apparently similar group that does not.

There has been only one large study that compared
the flu vaccine with a placebo for two random groups of older people in which neither the patients nor the scientists knew
which group was receiving which injection. It came to a different conclusion from the observational studies. Conducted by
Dutch researchers and published in 1994 in The Journal of the American Medical Association, it found that in those 60 to 69,
the vaccine prevented influenza about 57 percent of the time. In those over 70, the vaccine prevented the flu just 23 percent
of the time, though the estimate is imprecise because the study was not designed to look at this age group.

Because of this failure to rely upon the placebo-controlled
trials, which are considered the gold standard in medical evidence, health policy was based flawed studies."I think the evidence base we have leaned on is not valid," said Lone Simonsen, an epidemiologist and visiting
professor at the George Washington University School of Public Health and Health Services in Washington who was not connected
with the Lancet study.

In 2005, Dr. Simonsen, who was then at the National Institute
of Allergy and Infectious Diseases in Bethesda, Md., published a paper in The Archives of Internal Medicine that found something
odd: even though the percentage of older people who got an annual flu shot more than tripled from 1980 to 2001, there was
no corresponding drop in the death rate. That paper included one of the
first estimates of how many deaths are actually caused by the flu - a number hard to pin down because doctors seldom confirm
flu in their patients with lab tests. Using a statistical model and the best available data, Dr. Simonsen found that influenza
probably causes just 5 to 10 percent of all winter deaths in the elderly. But earlier studies had found that the flu vaccine
cut an elderly person's risk of dying by 50 percent.

"You don't have to do a whole lot of math to realize that
doesn't add up," said Dr. Lisa A. Jackson of the Group Health Center for Health Studies in Seattle, who has also studied the
effectiveness of the flu vaccine in the elderly.

Dr. Jackson at first tried to tease out underlying differences
between vaccinated and unvaccinated elderly people by using medical codes - a numerical shorthand that doctors use to classify
and record what is wrong with their patients. She and other researchers reasoned that patients with codes for cancer or heart
disease, for example, might be very sick, thus skewing the results. When they adjusted for those codes, however, the differences
between the vaccinated and unvaccinated groups became even more pronounced. The vaccine looked even more protective.

It was Michael L. Jackson's thesis project, at the University
of Washington, that revealed the flaw in using the codes to differentiate patients. For
the project, Mr. Jackson (no relation to Lisa Jackson) and three other researchers spent almost three years reading medical
charts and examining X-rays. They discovered that health-conscious people were more likely to get medical codes for things
like heart disease and cancer simply because they went to the doctor more often. But when Mr. Jackson adjusted for measures
of frailty - things like lung function, whether people needed help bathing or dressing, and what kinds of medications they
took - he found that vaccination had little effect on older people's risk for pneumonia, the most dangerous complication of
the flu.

That finding has a biological basis. Vaccines work by priming
the immune system to recognize and respond to incoming threats. Because the immune system slows down with age, older adults
do not respond as well to vaccines as younger adults. A recent study by
Dr. Wilbur H. Chen and colleagues at the Center for Vaccine Development at the University of Maryland School of Medicine found
that elderly participants needed four times the amount of antigens given in a standard dose of the flu vaccine to have the
same kind of immune response as healthy adults under 40. They presented their findings in May at the Annual Conference on
Vaccine Research in Baltimore.

Despite these findings, Dr. Shay said the C.D.C. had no
plans to change its vaccine recommendations, though he added that the agency had financed studies to look for more effective
influenza vaccines for the elderly.

Dr. Simonsen, the epidemiologist at George Washington,
said the new research made common-sense infection-control measures - like avoiding other sick people and frequent hand washing
- more important than ever. Still, she added, "The vaccine is still important. Thirty
percent protection is better than zero percent."

Cochrane Library
publishes the Cochrane Review, an
international evidence based group often doing meta-analysis of first
quality. It is one of the very few sources
for organizations that looks to the evidence, is neither run by the marketing
departments of drug companies are receiving pay therefrom. Every year they publish studies design to
guide the medical community away from serious errors. In much of the world state funds are used to
make the Cochrane Review free to the people.
Only Wyoming
provide such access in the U.S.

Study: No hard evidence that flu vaccine
protects the elderly

After a detailed analysis of 75 scientific
studies, a group of researchers
at the Cochrane Library has concluded that there's little hard evidence to
prove that the annual flu vaccination campaign for the elderly does any good.

The vaccine won't work unless it's
particularly well matched to the flu
strains in circulation, say the researchers. Some of the elderly don't respond
to the vaccine at all, and the most vulnerable often don't bother to get a
shot. And the data on flu rates in older people is often badly skewed by
ailments that have the same symptoms as flu but aren't affected by vaccine at
all.

The analysis drew considerable attention
in the U.K., where the government pays
about 150 million pounds a year to vaccinate three quarters of the older
population. Officially, the government estimates that the flu kills about
12,000 people a year in England.
But the Cochrane group says there really are no good estimates available
and the government figure is probably far too high.

"As the evidence is so scarce at the
moment, we should be looking at
other strategies to complement vaccinations," notes Tom Jefferson of the
Cochrane Collaboration in Rome.
"Some of these are very simple things like personal hygiene, and adequate
food and water. Meanwhile, we need to undertake a high quality, publicly funded
trial that runs over several seasons to try to resolve some of the
uncertainties we're currently facing."

There's been widespread recognition
among vaccine manufacturers that the
currently available vaccines are least effective in the elderly. And there are
a number of new programs underway to design a vaccine that can protect this
patient population.

Vaccines
for preventing seasonal influenza and its complications in people aged 65 or
older

Abstract

Background

Vaccines have been the
main global weapon to minimise the impact of influenza in the elderly for the
last four decades and are recommended worldwide for individuals aged 65 years
or older. The primary goal of influenza
vaccination in the elderly is to reduce the risk of complications among persons
who are most vulnerable.

Objectives

To assess the
effectiveness of vaccines in preventing influenza, influenza-like illness
(ILI), hospital admissions, complications and mortality in the elderly.
To identify and appraise comparative studies evaluating the effects of
influenza vaccines in the elderly.
To document types and frequency of adverse effects associated with influenza
vaccines in the elderly.

Selection
criteria

Randomised controlled
trials (RCTs), quasi-RCTs, cohort and case-control studies assessing efficacy
against influenza (laboratory-confirmed cases) or effectiveness against
influenza-like illness (ILI) or safety. Any influenza vaccine given
independently, in any dose, preparation or time schedule, compared with placebo
or with no intervention was considered.

Data collection and
analysis

We grouped reports first
according to the setting of the study (community or long-term care facilities)
and then by level of viral circulation and vaccine matching. We further
stratified by co-administration of pneumococcal polysaccharide vaccine (PPV)
and by different types of influenza vaccines. We analysed the following
outcomes: influenza, influenza-like illness, hospital admissions, complications
and deaths.

Main results

We included 75 studies.
Overall we identified 100 data sets. We identified one RCT assessing efficacy
and effectiveness. Although this seemed to show
an effect against influenza symptoms it was underpowered to detect any effect
on complications (1348 participants). The
remainder of our evidence base included non-RCTs. Due to the general low
quality of non-RCTs and the likely presence of
biases, {funded by and edited by the
drug company} which make interpretation of these data difficult and any firm conclusions
potentially misleading, we were unable to reach clear conclusions about the
effects of the vaccines in the elderly.

Authors' conclusions

The available evidence is
of poor quality and provides no guidance regarding the safety, efficacy or
effectiveness of influenza vaccines for people aged 65 years or older. To
resolve the uncertainty, an adequately powered publicly-funded randomised,
placebo-controlled trial run over several seasons should be undertaken.